Indocyanine green labels an orthotopic nude-mouse model of very-early colon-cancer liver metastases

Yoshihiko Tashiro, Hannah M. Hollandsworth, Hiroto Nishino, Jun Yamamoto, Siamak Amirfakhri, Filemoni Filemoni, Norihiko Sugisawa, Takeshi Aoki, Masahiko Murakami, Robert M. Hoffman, Michael Bouvet

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background/Aim: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) is used to visualize colon-cancer liver metastases (CCLM) during surgery. The present study aimed to use ICG to visualize small CCLM in an orthotopic mouse model. Materials and Methods: A 3-mm fragment of HT29 human colon cancer was implanted to the liver of 5 athymic nude mice (nu/nu). The Pearl Trilogy Small Animal Fluorescence Imaging system was used 24 h after intravenous (IV) injection of 0.025 mg (0.25 mg/ml) ICG. Results: In four of the five mice, tumor fluorescence was detected. Small tumors (approximately 3 mm) were distinctly visualized with a minimal fluorescence liver signal, with a mean tumor to liver signal ratio of 1.81 (SD±0.167). Conclusion: Small CCLM can be clearly identified by ICG fluorescence in an orthotopic nude-mouse model. This model is translatable to the clinic for the detection of occult early CCLM. Indocyanine green (ICG) fluorescence imaging is widely applied in various surgical fields. In liver surgery, ICG fluorescence imaging is used in tumor detection, tattooing, biliary-tract contrast, liver segmentation and determination of surgical margins (1-3). Laparoscopic liver resection has become popular in recent years; however, palpation and visualization of liver tumors is difficult in laparoscopic surgery. Therefore, the identification of liver tumors using ICG fluorescence signals is an extremely useful tool in laparoscopic liver surgery. The most frequently used imaging modalities to assess liver tumors are computed tomography (CT) and intra-operative ultrasonography (IOUS). However, even with the combined use of these modalities, 6% to 20% of liver metastases are not identified (4-6). This may lead to inadequate assessment of the extent of disease and incomplete resection, which can have a significant impact on outcomes and prognosis (7). Ishizawa et al. have shown that primary hepatocellular carcinoma and colorectal-cancer liver metastases could be identified using near-infrared (NIR) fluorescence imaging (8). Currently, NIR fluorescence imaging is becoming more widely used in the operative setting for the identification of hepatic pathology and anatomy. Fluorescence imaging with ICG of colon-cancer liver metastases (CCLM) in rat models has been previously established (9). The present study aimed to develop an orthotopic nude-mouse model for fluorescence visualization of early and small CCLM using ICG.

Original languageEnglish
Pages (from-to)2277-2280
Number of pages4
JournalIn Vivo
Volume34
Issue number5
DOIs
Publication statusPublished - 2020 Oct
Externally publishedYes

Keywords

  • Colon cancer
  • Detection
  • Fluorescence
  • ICG
  • Liver metastasis
  • Orthotopic mouse model

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

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